Subjects with histories of opioid abuse were studied on the Residential Research Unit to investigate the effects of nalmefene, a new investigational opioid antagonist with relatively few agonist effects. This research should be useful in determining the possible utility of this long-acting (several days) opioid antagonist for the treatment of opioid dependent persons. This research is being conducted in collaboration with the Chemistry and Drug Metabolism Laboratory and the Research Support Branch. Two studies were planned, the first will assess the abuse liability of nalmefene and the second will determine the efficacy of nalmefene to block the subjective and physiological effects of morphine. The first study has been completed. Results indicated that nalmefene did not produce typical opiate-like abuse liability, but that side effects, such as feelings of agitation and irritability, muscle tension, headache, and insomnia may limit its use as possible treatment for opioid dependence. The second study was recently completed, and the data are currently being analyzed. A preliminary report will be presented at the 1991 meeting of the Committee on Problems of Drug Dependence.